A pesticide used for decades in agriculture may be linked to a much greater risk of Parkinson’s disease, and scientists have uncovered a possible explanation for how it damages the brain.
Researchers at UCLA Health found that people with long-term residential exposure to chlorpyrifos, a widely used pesticide, had more than 2.5 times the risk of developing Parkinson’s disease compared with those who were not exposed. Laboratory experiments also revealed how the chemical can interfere with the brain’s ability to remove damaged proteins, leading to the loss of nerve cells essential for controlling movement.
The study, published in Molecular Neurodegeneration, goes beyond identifying a connection between pesticide exposure and Parkinson’s. By examining what happens inside affected brain cells, the researchers uncovered a biological mechanism that could eventually provide new ways to protect the brain from damage.
A Common Pesticide With a Troubling Link to Parkinson’s
Parkinson’s disease affects nearly one million Americans. The progressive neurological condition gradually damages brain cells involved in movement, often causing tremors, muscle stiffness, slowed movement, and difficulties with coordination.
One of the defining features of Parkinson’s is the loss of neurons that produce dopamine. This chemical messenger allows nerve cells to communicate and helps the brain coordinate smooth, controlled movements. As dopamine levels decline, the brain becomes less capable of regulating those movements.
Although inherited genetic factors can influence who develops Parkinson’s, researchers have increasingly focused on environmental exposures that may also contribute to the disease. Pesticides are of particular interest because some chemicals used to kill insects or other agricultural pests can also interfere with biological processes in the nervous system.
Chlorpyrifos has been used extensively in agriculture for decades. Its residential use was banned in the United States in 2001, and agricultural applications faced additional restrictions in 2021. However, the pesticide remains in use on many crops in the United States and continues to be widely applied in other countries.
Because exposure may have occurred years before symptoms appeared, understanding the potential long-term effects of chlorpyrifos is particularly important. Identifying specific chemicals associated with Parkinson’s could help researchers develop prevention strategies and determine whether previously exposed individuals might benefit from additional neurological monitoring.
Researchers Find More Than Double the Parkinson’s Risk
To investigate the connection, UCLA scientists examined information from 829 people diagnosed with Parkinson’s disease and 824 people without the condition. All participants were enrolled in the university’s long-running Parkinson’s Environment and Genes study, which investigates how environmental exposures and inherited factors influence Parkinson’s risk.
The researchers combined California’s detailed pesticide application records with participants’ residential and workplace address histories. This allowed them to estimate how much chlorpyrifos individuals may have encountered over time based on where they lived and worked.
The results revealed a striking association. People with prolonged residential exposure to chlorpyrifos had more than 2.5 times the risk of Parkinson’s disease compared with those who had no such exposure.
Although this population analysis could not establish that the pesticide directly caused Parkinson’s, the researchers took an additional step to investigate whether chlorpyrifos could produce the kinds of brain damage seen in people with the disease.
How the Pesticide Damages Brain Cells
The team exposed mice to chlorpyrifos in aerosol form for 11 weeks. The inhalation approach was designed to resemble a common way people may encounter pesticides in the environment.
The exposed mice developed movement difficulties and lost neurons responsible for producing dopamine. This was particularly significant because the degeneration of these same nerve cells is a central feature of Parkinson’s disease.
The researchers also detected inflammation in the animals’ brains, along with abnormal accumulations of a protein called alpha-synuclein.
Under normal conditions, alpha-synuclein is found in nerve cells and plays a role in their functioning. However, the protein can accumulate in abnormal clumps that are closely associated with Parkinson’s disease. These deposits are a major focus of research into why certain brain cells gradually deteriorate.
Together, the findings showed that chlorpyrifos exposure could reproduce several important characteristics of Parkinson’s in laboratory animals, strengthening the biological evidence behind the human population findings.
Scientists Uncover a Breakdown in the Brain’s Cleanup System
The researchers then turned to zebrafish to investigate exactly how chlorpyrifos harms neurons. These small fish are frequently used in neuroscience research because they allow scientists to study biological processes involved in nerve cell development and survival.
Their experiments pointed to a disruption in autophagy, a natural cellular maintenance process that helps remove damaged proteins and other unwanted material.
Autophagy functions much like an internal recycling system. Cells use it to break down worn-out or defective components so that potentially harmful material does not accumulate. This process is especially important for neurons, many of which must remain functional throughout a person’s lifetime.
When chlorpyrifos interfered with this cleanup system, damaged material accumulated inside neurons, contributing to their deterioration.
The researchers also made an encouraging discovery. When they restored the cellular cleanup process or removed synuclein protein in their experiments, the neurons were protected from damage.
This finding suggests that the pesticide’s harmful effects may depend partly on a biological pathway that researchers could potentially target with future treatments.
A Potential New Strategy for Protecting Against Parkinson’s
The discovery raises the possibility of developing therapies that strengthen the brain’s cellular cleanup mechanisms and help protect vulnerable neurons. Such treatments might eventually prove useful for people exposed to chlorpyrifos or other pesticides that disrupt similar processes.
However, the protective effects have so far been demonstrated in laboratory models. Additional research will be needed to determine whether enhancing autophagy can prevent or reduce pesticide-related brain damage in humans.
Scientists also want to investigate whether other commonly used pesticides interfere with the same cellular mechanisms. Although chlorpyrifos use has declined in the United States, many people were exposed before restrictions were introduced, and related agricultural chemicals remain widely used.
The findings could also help identify people with a history of substantial pesticide exposure who may benefit from closer neurological monitoring. Earlier recognition of possible changes in brain function could become increasingly important as researchers work toward treatments that slow or prevent Parkinson’s progression.
Dr. Jeff Bronstein, professor of Neurology at UCLA Health and the study’s senior author, emphasized the importance of identifying a particular chemical rather than treating all pesticides as a single category.
“This study establishes chlorpyrifos as a specific environmental risk factor for Parkinson’s disease, not just pesticides as a general class,” said Dr. Jeff Bronstein.
“By showing the biological mechanism in animal models, we’ve demonstrated that this association is likely causal. The discovery that autophagy dysfunction drives the neurotoxicity also points us toward potential therapeutic strategies to protect vulnerable brain cells.”